ArticlePLoS computational biology2012
Epitope flexibility and dynamic footprint revealed by molecular dynamics of a pMHC-TCR complex.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Article
- Quantifying conformational changes in the TCR:pMHC-I binding interface.Frontiers in immunology · 2024Article
- Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease.Nature communications · 2023Article
- Molecular Dynamics Methods for Antibody Design.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Advancing therapies for viral infections using mechanistic computational models of the dynamic interplay between the virus and host immune response.Current opinion in virology · 2021Review
- Intrinsic Disorder in the T Cell Receptor Creates Cooperativity and Controls ZAP70 Binding.Biophysical journal · 2021Article
- Peptide cargo tunes a network of correlated motions in human leucocyte antigens.The FEBS journal · 2020Article
- T cell receptor interactions with human leukocyte antigen govern indirect peptide selectivity for the cancer testis antigen MAGE-A4.The Journal of biological chemistry · 2020Article
- Methods for sequence and structural analysis of B and T cell receptor repertoires.Computational and structural biotechnology journal · 2020Review
- The Role of Conformational Dynamics in Abacavir-Induced Hypersensitivity Syndrome.Scientific reports · 2019Article
- Article
- How peptide/MHC presence affects the dynamics of the LC13 T-cell receptor.Scientific reports · 2019Article
- Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections.Frontiers in immunology · 2019Review
- Integrating Experiment and Theory to Understand TCR-pMHC Dynamics.Frontiers in immunology · 2018Review
- Article
- Structure-based Methods for Binding Mode and Binding Affinity Prediction for Peptide-MHC Complexes.Current topics in medicinal chemistry · 2018Review
- The Hypervariable Loops of Free TCRs Sample Multiple Distinct Metastable Conformations in Solution.Frontiers in molecular biosciences · 2018Article
- Dynamical footprint of cross-reactivity in a human autoimmune T-cell receptor.Scientific reports · 2017Article
- Exploration of the Conformational Dynamics of Major Histocompatibility Complex Molecules.Frontiers in immunology · 2017Review
- Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation.Frontiers in immunology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The crystal structures of unliganded and liganded pMHC molecules provide a structural basis for TCR recognition yet they represent 'snapshots' and offer limited insight into dynamics that may be important for interaction and T cell activation. MHC molecules HLA-B*3501 and HLA-B*3508 both bind a 13 mer viral peptide (LPEP) yet only HLA-B*3508-LPEP induces a CTL response characterised by the dominant TCR clonetype SB27. HLA-B*3508-LPEP forms a tight and long-lived complex with SB27, but the relatively weak interaction between HLA-B*3501-LPEP and SB27 fails to trigger an immune response. HLA-B*3501 and HLA-B*3508 differ by only one amino acid (L/R156) located on α2-helix, but this does not alter the MHC or peptide structure nor does this polymorphic residue interact with the peptide or SB27. In the absence of a structural rationalisation for the differences in TCR engagement we performed a molecular dynamics study of both pMHC complexes and HLA-B*3508-LPEP in complex with SB27. This reveals that the high flexibility of the peptide in HLA-B*3501 compared to HLA-B*3508, which was not apparent in the crystal structure alone, may have an under-appreciated role in SB27 recognition. The TCR pivots atop peptide residues 6-9 and makes transient MHC contacts that extend those observed in the crystal structure. Thus MD offers an insight into 'scanning' mechanism of SB27 that extends the role of the germline encoded CDR2α and CDR2β loops. Our data are consistent with the vast body of experimental observations for the pMHC-LPEP-SB27 interaction and provide additional insights not accessible using crystallography.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.